Latent HIV Infection of BBB Pericytes Enhances Gap Junction-mediated Crosstalk with Endothelial Cells.
7 affiliations
- 1Department of Biochemistry and Molecular Biology, University of Miami Leonard M. Miller School of Medicine, Suite 528, 1011 NW 15Th Street, Miami, FL, 33136, USA. [email protected].
- 2Department of Biochemistry and Molecular Biology, University of Miami Leonard M. Miller School of Medicine, Suite 528, 1011 NW 15Th Street, Miami, FL, 33136, USA.
- 3Medical Scientist Training Program, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA.
- 4Sylvester Comprehensive Cancer Center, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA.
- 5Department of Pharmacology & Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
- 6Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USA.
- 7Department of Biochemistry and Molecular Biology, University of Miami Leonard M. Miller School of Medicine, Suite 528, 1011 NW 15Th Street, Miami, FL, 33136, USA. [email protected].
Abstract
HIV-Associated Neurocognitive Impairments persist, with over 50% of patients experiencing cognitive decline. Blood-brain barrier (BBB) impairment is a consistent feature of this comorbidity, which is remarkable, because BBB endothelial cells are not productively infected by HIV-1. Conversely, pericytes can be productively infected with HIV-1 and are essential for cerebrovascular homeostasis. Given this, we hypothesized that HIV-1 infection of pericytes disrupts BBB endothelial cell integrity through dysfunctional gap junction and hemichannel signaling, impairing pericyte-endothelial intercellular communication. Using a co-culture model with primary human BBB pericytes and brain microvascular endothelial cells, pericytes were infected with HIV-1 for 3 or 7 days, exhibiting active and latent viral phenotypes. Findings revealed enhanced gap junction communication between HIV-infected pericytes and endothelial cells under both conditions, and blocking gap junctions modulated endothelial inflammatory responses. Overall, this study advances our understanding of the molecular mechanisms underlying HIV-associated BBB dysfunction and may inform the development of targeted therapeutic strategies.
Related
- Andrographolide Promotes Post-Ischemic Endothelial Angiogenic Activity via IL-10-Mediated M2-Like Microglia-Endothelial Crosstalk Involving Endothelial VEGFR2 Upregulation.
- SPP1-CD44-Mediated Crosstalk Between Endothelial and Macrophage Subpopulations Promotes Pancreatic Ductal Adenocarcinoma Progression Through S100A6 Upregulation
- Immune-endothelial crosstalk at the nexus of neuroinflammation and vascular dysfunction in aging
- Ginseng-Sanqi-Chuanxiong extract ameliorates hypertensive vascular aging through endothelial–smooth muscle cell crosstalk via the PPARγ/NF-κB axis
- Neuro‐associated SEMA3C+ tumour cells promote gastric cancer peritoneal metastasis via EBF2–FGF7–FGFR2‐mediated tumour–endothelial crosstalk
BibTeX
@article{schmidlin2026latent,
title = {{Latent HIV Infection of BBB Pericytes Enhances Gap Junction-mediated Crosstalk with Endothelial Cells.}},
author = {Sarah Schmidlin and Oandy Naranjo and Silvia Torices and Nikolai Fattakhov and Monika Gilicinska and Masha Minevich and Kyra A Schindler and Destiny Tiburcio and Olivia M Osborne and Arpan Acharya and Minseon Park and Mario Stevenson and Siddappa N Byrareddy and Michal Toborek},
journal = {Molecular neurobiology},
year = {2026},
month = oct,
doi = {10.1007/s12035-026-06266-0},
url = {https://europepmc.org/article/MED/42886426},
note = {CC BY},
}
RIS
TY - JOUR
TI - Latent HIV Infection of BBB Pericytes Enhances Gap Junction-mediated Crosstalk with Endothelial Cells.
AU - Sarah Schmidlin
AU - Oandy Naranjo
AU - Silvia Torices
AU - Nikolai Fattakhov
AU - Monika Gilicinska
AU - Masha Minevich
AU - Kyra A Schindler
AU - Destiny Tiburcio
AU - Olivia M Osborne
AU - Arpan Acharya
AU - Minseon Park
AU - Mario Stevenson
AU - Siddappa N Byrareddy
AU - Michal Toborek
PY - 2026
DA - 2026/10/16
JO - Molecular neurobiology
DO - 10.1007/s12035-026-06266-0
UR - https://europepmc.org/article/MED/42886426
AB - HIV-Associated Neurocognitive Impairments persist, with over 50% of patients experiencing cognitive decline. Blood-brain barrier (BBB) impairment is a consistent feature of this comorbidity, which is remarkable, because BBB endothelial cells are not productively infected by HIV-1. Conversely, pericytes can be productively infected with HIV-1 and are essential for cerebrovascular homeostasis. Given this, we hypothesized that HIV-1 infection of pericytes disrupts BBB endothelial cell integrity through dysfunctional gap junction and hemichannel signaling, impairing pericyte-endothelial intercellular communication. Using a co-culture model with primary human BBB pericytes and brain microvascular endothelial cells, pericytes were infected with HIV-1 for 3 or 7 days, exhibiting active and latent viral phenotypes. Findings revealed enhanced gap junction communication between HIV-infected pericytes and endothelial cells under both conditions, and blocking gap junctions modulated endothelial inflammatory responses. Overall, this study advances our understanding of the molecular mechanisms underlying HIV-associated BBB dysfunction and may inform the development of targeted therapeutic strategies.
SN - 0893-7648
SN - 1559-1182
ER -